It is proposed to continue the investigation of the biosynthesis of the antileukemic alkaloids of Cephalotaxus plants. There are three major objectives to this research. The first is to elucidate the mode of biosynthesis of the parent alkaloid cephalotaxine from phenylalanine and tyrosine. This will be accomplished by administration of specifically labeled precursors to Cephalotaxus plants and to tissue cultures of Cephalotaxus followed by appropriate degradations. The second objective is the further clarification of the steps in the biosynthesis of the diacids which are attached to cephalotaxine in deoxyharringtonine, harringtonine, and isoharringtonine. This part of the investigation will rely on the administration of specifically labeled precursors to Cephalotaxus plants with subsequent degradative work. The third objective is to examine the metabolic relationships between the four antileukemic ester alkaloids: deoxyharringtonine, harringtonine, isoharringtonine, and homoharringtonine. This work will rely upon administration of labeled precursors to tissue cultures and upon short-term exposure of Cephalotaxus plants to a steady-state concentration of 14C-carbon dioxide.